Thalamic deep brain stimulation for Tourette Syndrome: A naturalistic trial with brief randomized,double-blinded sham-controlled periods

BackgroundThere is still a lack of controlled studies to prove efficacy of thalamic deep brain stimulation for Tourette's Syndrome.ObjectivesIn this controlled trial, we investigated the course of tic severity, comorbidities and quality of life during thalamic stimulation and whether changes in tic severity can be assigned to ongoing compared to sham stimulation.MethodsWe included eight adult patients with medically refractory Tourette's syndrome. Bilateral electrodes were implanted in the centromedian-parafascicular-complex and the nucleus ventro-oralis internus. Tic severity, quality of life and comorbidities were assessed before surgery as well as six and twelve months after. Short randomized, double-blinded sham-controlled crossover sequences with either active or sham stimulation were implemented at both six- and twelve-months’ assessments. The primary outcome measurement was the difference in the Yale Global Tic Severity Scale tic score between active and sham stimulation. Adverse events were systematically surveyed for all patients to evaluate safety.ResultsActive stimulation resulted in significantly higher tic reductions than sham stimulation (F = 79.5; p = 0.001). Overall quality of life and comorbidities improved significantly in the open-label-phase. Over the course of the trial two severe adverse events occurred that were resolved without sequelae.ConclusionOur results provide evidence that thalamic stimulation is effective in improving tic severity and overall quality of life. Crucially, the reduction of tic severity was primarily driven by active stimulation. Further research may focus on improving stimulation protocols and refining patient selection to improve efficacy and safety of deep brain stimulation for Tourette's Syndrome.     

Subthalamic nucleus deep brain stimulation improves sleep in Parkinson's disease patients: a retrospective study and a meta-analysis

BackgroundMost Parkinson's patients suffered from sleep problems. There is increasing evidence that Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) has a positive effect on several sleep parameters, improving overall sleep quality in patients with PD. However, the results are controversial.MethodsWe performed a retrospective study and meta-analysis to assess the Parkinson's disease sleep scale (PDSS) in Parkinson's patients.ResultsWe reviewed our data of patients who underwent STN-DBS, and then extracted five other trials to perform a meta-analysis. The pooled results showed an advantage on post-operative PDSS in both our medical center and pooled results (MD = 20.41, 95% CI = [13.03, 27.79], I² = 61%, P < 0.001). There was a significant difference in Unified Parkinson's Disease Rating Scale (UPDRS)-Ⅲ score between pre and post-operation (MD = −12.59, 95% CI = [−14.70, −10.49], I² = 90%, P < 0.001). What's more, Parkinsonian medication was significantly lower in the post-operative groups after DBS (MD = −314.71, 95% CI = [−468.13, −161.28], I² = 53%, P < 0.001).ConclusionIn the retrospective study and meta-analysis of 6 trials, we found that DBS can significantly increase sleep quality. Furthermore, motor function improved and Parkinsonian medication was significantly decreased postoperatively. The sample size was enough and no further investigations would change the conclusion.     

Neurophysiologisches Monitoring in der funktionellen Neurochirurgie bei Bewegungsstörungen: Intraoperative Mikroelektrodenableitungen

Intraoperative microelectrode recordings serve as an exploratory guide for many stereotactic neurosurgeons in order to objectively localize deep brain sites to be operated for the control of movement disorders. In this context, microelectrode recordings are used to (i) map structural boundaries, (ii) provide a physiologic delineation of the sensorimotor territory within the surgical target and (iii) to identify and localize neuronal activities related to pathologic brain function such as tremor or dystonia. This article provides an overview of discharge characteristics of single cell activity in the three most common targets for movement disorder surgery: subthalamic nucleus (STN), pars interna of the globus pallidus (GPi) and thalamic nucleus ventro-intermedius (Vim).     

Restoration of functional network state towards more physiological condition as the correlate of clinical effects of pallidal deep brain stimulation in dystonia

BackgroundDeep brain stimulation of the internal globus pallidus (GPi DBS) is an invasive therapeutic modality intended to retune abnormal central nervous system patterns and relieve the patient of dystonic or other motor symptoms.ObjectivesThe aim of the presented research was to determine the neuroanatomical signature of GPi DBS modulation and its association with the clinical outcome.MethodsThis open-label fixed-order study with cross-sectional validation against healthy controls analysed the resting-state functional MRI activity changes induced by GPi DBS in 18 dystonia patients of heterogeneous aetiology, focusing on both global (full brain) and local connectivity (local signal homogeneity).ResultsCompared to the switched-off state, the activation of GPi DBS led to the restoration of global subcortical connectivity patterns (in both putamina, diencephalon and brainstem) towards those of healthy controls, with positive direct correlation over large-scale cortico-basal ganglia-thalamo-cortical and cerebellar networks with the clinical improvement. Nonetheless, on average, GPi DBS also seemed to bring local connectivity both in the cortical and subcortical regions farther away from the state detected in healthy controls. Interestingly, its correlation with clinical outcome showed that in better DBS responders, local connectivity defied this effect and approached healthy controls.ConclusionsAll in all, the extent of restoration of both these main metrics of interest towards the levels found in healthy controls clearly correlated with the clinical improvement, indicating that the restoration of network state towards more physiological condition may be a precondition for successful GPi DBS outcome in dystonia.     

Characteristics of globus pallidus internus local field potentials in generalized dystonia patients with TWNK mutation

ObjectiveWe focused on a rare gene mutation causing dystonia in two siblings who received globus pallidus internus deep brain stimulation (GPi-DBS). The aim was to characterize the relationship between neuronal activity patterns and clinical syndromes.MethodsWhole exome sequencing was applied to identify the TWNK (previous symbol C10orf2) mutation; Two siblings with TWNK mutation presented as generalized dystonia with rigidity and bradykinesia; four other sporadic generalized dystonia patients underwent GPi-DBS and local field potentials (LFPs) were recorded. Oscillatory activities were illustrated with power spectra and temporal dynamics measured by the Lempel-Ziv complexity (LZC).ResultsNormalized power spectra of GPi LFPs differed between patients with TWNK mutation and dystonia over the low beta bands. Patients with TWNK mutation had higher low beta power (15–27 Hz, unpaired t-test, corrected P < 0.0022) and lower LZC (15–27 Hz, unpaired t-test, P < 0.01) than other patients with generalized dystonia. On the other hand, the TWNK mutation patients showed decreased low frequency and beta oscillation in the GPi after DBS, as well as improved movement performance.ConclusionThe LFPs were different in TWNK mutation dystonia siblings than other patients with generalized dystonia, which indicate the abnormal LFPs were related to symptoms rather than specific disease. In addition, the inhibited effect on oscillations also provided a potential evidence for DBS treatment on rare movement disorders.SignificanceThis study could potentially aid in the future development of adaptive DBS via rare disease LFPs comparison.     

Hallervorden?Spatz病:三例报告并文献复习简

目的探讨Hallervorden—Spatz病之临床和影像学特点。方法与结果回顾分析3例Hallervorden—Spatz病患者临床资料。其中2例临床表现为锥体外系症状,影像学符合典型“虎眼征”,诊断明确;1例阳性体征为痉挛步态伴严重构音障碍,锥体外系症状不典型,缺乏不自主动作,T2WI显示典型“虎眼征”,20年后复查时双侧苍白球前内侧高信号区明显缩小,符合不典型Hallervorden—Spatz病。结论典型Hallervorden—Spatz病儿童期发病、病程短,可根据以锥体外系症状为主的临床体征和T2WI显示典型“虎眼征”而获得早期诊断;非典型Hallervorden．Spatz病青少年期发病、病程长,锥体外系症状可不典型,T2WI“虎眼征”可随病程出现动态变化。     

Regionally selective atrophy of subcortical structures in prodromal HD as revealed by statistical shape analysis

Huntington disease (HD) is a neurodegenerative disorder that involves preferential atrophy in the striatal complex and related subcortical nuclei. In this article, which is based on a dataset extracted from the PREDICT‐HD study, we use statistical shape analysis with deformation markers obtained through “Large Deformation Diffeomorphic Metric Mapping” of cortical surfaces to highlight specific atrophy patterns in the caudate, putamen, and globus pallidus, at different prodromal stages of the disease. On the basis of the relation to cortico‐basal ganglia circuitry, we propose that statistical shape analysis, along with other structural and functional imaging studies, may help expand our understanding of the brain circuitry affected and other aspects of the neurobiology of HD, and also guide the most effective strategies for intervention. Hum Brain Mapp 35:792–809, 2014. © 2012 Wiley Periodicals, Inc.     

Deep Brain Stimulation: Overview And Update

Objective: To summarize the techniques for physiological localization that contribute to increased accuracy in the surgical treatment of movement disorders. Methods: Initial targeting through imaging referenced to stereotactic atlas are confirmed through physiological localization. Spontaneous recording, elicited recording, evoked potentials and stimulation provided physiological localization for target confirmation in the placement of lesions or DBS. Results: Imaging and stereotactic techniques produce inaccuracy that may be address by physiological localization. Microelectrode recording from basal ganglia and thalamic sites provides signature neuronal patterns to confirm and guide the trajectory. Spontaneous and elicited neuronal response are recorded from microelectrodes. Conclusions: Accuracy of movement disorders surgery is enhance through use of physiological localization. A multimodality approach provides techniques that allow localization in a variety of patient and environmental conditions.